6th Annual Symposium
Physics of Cancer
September 7-9, 2015
|PoC - Physics of Cancer - Annual Symposium|
Mechanosensory response to intercellular invasion
Johns Hopkins University, 725 N. Wolfe Street 818 PCTB Baltimore, MD 21205, USA
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During metastasis, cancer cells utilize F-actin-based membrane protrusions, called invadopodia, to invade and migrate through basement membrane. In normal biological processes, F-actin-based structures similar to invadopodia, known as podosomes, have been shown to mediate cell adhesion and migration in cultured cells. My lab has discovered an essential function for invasive podosome-like structures in muscle cell fusion in vivo. We show that during myoblast fusion, in which mononucleated muscle cells fusion to form multinucleated muscle fibers, one population of muscle cells (the attacking cells) invade their fusion partners (the receiving cells) with podosome-like structures to promote fusion pore formation. We further reveal that the receiving cell mounts a Myosin II-mediated mechanosensory response to the podosome invasion from the attacking cell, leading to Myosin II accumulation to the muscle cell contact site, known as the fusogenic synapse. Interestingly, accumulation of Myosin II in the receiving cell still occurs in the absence of chemical signaling initiated by the cell adhesion molecule in the receiving cell, suggesting that Myosin II functions as a mechanosensor for intercellular invasion. Using micropipette aspiration (MPA) and atomic force microscopy (AFM), we show that Myosin II is required for enhancing cortical tension/stiffness in the receiving cell. Our work has established a biophysical framework for intercellular fusion – the pushing forces from the attacking cell and the resisting forces from the receiving cell put the fusogenic synapse under high mechanical tension, which helps to bring the two apposing membranes into close proximity to facilitate fusogen engagement and membrane fusion.